Autoantibody cluster analysis in juvenile lupus nephritis

Clin Rheumatol. 2022 Aug;41(8):2375-2381. doi: 10.1007/s10067-022-06146-7. Epub 2022 Mar 28.

Abstract

Objective: Demographics, clinical features, and biomarkers do not consistently anticipate risk of end-stage renal disease (ESRD) in juvenile lupus nephritis (LN). Here, the existence of autoantibody clusters predictive of ESRD was explored in a cohort of biopsy-proven juvenile LN.

Methods: A retrospective chart review was performed of patients with juvenile systemic lupus erythematosus (jSLE) and biopsy-confirmed LN. Primary endpoints were ESRD and mortality. Patients were included for K-medians cluster analysis if they had a complete autoantibody profile, which included ANA titer, anti-dsDNA, anti-Smith, anti-RNP, anti-Ro/SSA, anti-La/SSB. Chi-square test was used for categorical variables and one-way ANOVA for continuous measures. Significance was p<0.05.

Results: Fifty-three met inclusion criteria, of which 45 were female and 37 were black. Over 80% developed LN within one year of jSLE onset and more than half (n=29) had LN at diagnosis of jSLE. Six developed ESRD. No mortalities were reported. Forty-six had a complete autoantibody profile, including four with ESRD. Three clusters were identified. Group 1 (n=8) was defined by anti-dsDNA; group 2 (n=28) by high-titer ANA (>1:1280), anti-Smith, anti-RNP, and anti-Ro/SSA; and group 3 (n=10) by anti-dsDNA and anti-Ro/SSA. There was no difference between the groups in demographics, jSLE manifestations, or markers of renal function. One in group 2 and three in group 3 developed ESRD. Those in group 3 were younger at diagnosis of LN (p=0.084) and had the highest frequency of ESRD (p=0.025).

Conclusion: Cluster analysis revealed the highest frequency of ESRD in the group with LN defined by anti-Ro/SSA and anti-dsDNA co-positivity. Key Points • Lupus nephritis commonly is present at diagnosis of juvenile systemic lupus erythematosus or develops within the first year. • End-stage renal disease was more frequent in the cluster defined by anti-dsDNA and anti-Ro/SSA co-positivity; patients with this profile may benefit from more aggressive immunosuppression.

Keywords: Anti-Ro/SSA; Cluster analysis; End-stage renal disease; Juvenile systemic lupus erythematosus; Lupus nephritis.

MeSH terms

  • Antibodies, Antinuclear / analysis
  • Autoantibodies / analysis
  • Biomarkers
  • Cluster Analysis
  • DNA
  • Female
  • Humans
  • Kidney Failure, Chronic* / epidemiology
  • Lupus Erythematosus, Systemic* / diagnosis
  • Lupus Nephritis* / diagnosis
  • Male
  • Retrospective Studies

Substances

  • Antibodies, Antinuclear
  • Autoantibodies
  • Biomarkers
  • DNA